Nicola Normanno1, Antonio Rossi2, Alessandro Morabito3, Simona Signoriello4, Simona Bevilacqua5, Massimo Di Maio6, Raffaele Costanzo3, Antonella De Luca5, Agnese Montanino3, Cesare Gridelli2, Gaetano Rocco7, Francesco Perrone6, Ciro Gallo4. 1. Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy. Electronic address: nicnorm@yahoo.com. 2. Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. 3. Medical Oncology Unit, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy. 4. Medical Statistics, Second University, Napoli, Italy. 5. Cell Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy. 6. Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy. 7. Division of Thoracic Surgery, Department of Thoracic Surgical and Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale" - IRCCS, Napoli, Italy.
Abstract
OBJECTIVES: Circulating tumor cells (CTCs) have been hypothesized to be a prognostic factor in small-cell lung cancer (SCLC), and different cutoffs have been proposed to identify patients at high risk. We assessed the prognostic value of CTCs in patients with extensive SCLC. MATERIALS AND METHODS: CTCs were assessed with the CellSearch system in 60 extensive SCLC patients. CTC count at baseline or after one cycle of chemotherapy (cycle-1) or as change after chemotherapy were analyzed separately. Primary outcome was overall survival. The accuracy of prognostic role was assessed by Harrell's c-index. "Optimal" cutoffs were derived by bootstrap resampling to reduce the overfitting bias; accuracy improvement was estimated by calculating the difference of c-indexes of models including clinical variables with or without CTCs. RESULTS: CTCs were identified in 90% (54/60) of patients at baseline, in which CTC count ranged from 0 to 24,281. CTC count was strongly associated with the number of organs involved. The prognostic accuracy was only marginally increased by the addition to clinical information of "optimal" CTC cutoffs at baseline and after cycle-1. Conversely, a reduction of CTC count higher than 89% following chemotherapy significantly improved prognostic accuracy (bootstrap p-value=0.009) and was associated with a lower risk of death (HR 0.24, 95% CI 0.09-0.61). When previously proposed cutoffs were applied to our cohort, they showed only marginal improvement of the prognostic accuracy. CONCLUSION: CTCs have useful prognostic role in extensive SCLC, but only the change of CTC count after the first cycle of chemotherapy provides clinically relevant information. Previously reported CTC cutoffs were not prognostic in our cohort of patients.
OBJECTIVES: Circulating tumor cells (CTCs) have been hypothesized to be a prognostic factor in small-cell lung cancer (SCLC), and different cutoffs have been proposed to identify patients at high risk. We assessed the prognostic value of CTCs in patients with extensive SCLC. MATERIALS AND METHODS: CTCs were assessed with the CellSearch system in 60 extensive SCLCpatients. CTC count at baseline or after one cycle of chemotherapy (cycle-1) or as change after chemotherapy were analyzed separately. Primary outcome was overall survival. The accuracy of prognostic role was assessed by Harrell's c-index. "Optimal" cutoffs were derived by bootstrap resampling to reduce the overfitting bias; accuracy improvement was estimated by calculating the difference of c-indexes of models including clinical variables with or without CTCs. RESULTS: CTCs were identified in 90% (54/60) of patients at baseline, in which CTC count ranged from 0 to 24,281. CTC count was strongly associated with the number of organs involved. The prognostic accuracy was only marginally increased by the addition to clinical information of "optimal" CTC cutoffs at baseline and after cycle-1. Conversely, a reduction of CTC count higher than 89% following chemotherapy significantly improved prognostic accuracy (bootstrap p-value=0.009) and was associated with a lower risk of death (HR 0.24, 95% CI 0.09-0.61). When previously proposed cutoffs were applied to our cohort, they showed only marginal improvement of the prognostic accuracy. CONCLUSION: CTCs have useful prognostic role in extensive SCLC, but only the change of CTC count after the first cycle of chemotherapy provides clinically relevant information. Previously reported CTC cutoffs were not prognostic in our cohort of patients.
Authors: Chandra P Belani; Suzanne E Dahlberg; Charles M Rudin; Martin Fleisher; Helen X Chen; Naoko Takebe; Mario R Velasco; William J Tester; Keren Sturtz; Christine L Hann; James C Shanks; Manish Monga; Suresh S Ramalingam; Joan H Schiller Journal: Cancer Date: 2016-05-10 Impact factor: 6.860
Authors: Marius Ilie; Véronique Hofman; Elodie Long; Olivier Bordone; Eric Selva; Kevin Washetine; Charles Hugo Marquette; Paul Hofman Journal: Ann Transl Med Date: 2014-11
Authors: Victoria Foy; Colin R Lindsay; Alexandra Carmel; Fabiola Fernandez-Gutierrez; Matthew G Krebs; Lynsey Priest; Mathew Carter; Harry J M Groen; T Jeroen N Hiltermann; Antonella de Luca; Francoise Farace; Benjamin Besse; Leon Terstappen; Elisabetta Rossi; Alessandro Morabito; Francesco Perrone; Andrew Renehan; Corinne Faivre-Finn; Nicola Normanno; Caroline Dive; Fiona Blackhall; Stefan Michiels Journal: Transl Lung Cancer Res Date: 2021-04